Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure
Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure
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DOI：
10.1016/s0006-291x(02)00487-4
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发表时间：
2002-06-07
影响因子：
3.1
通讯作者：
Garel, JM
中科院分区：
文献类型：
--
作者：
Cueille, C;Pidoux, E;Garel, JM
降钙素基因相关肽(CGRP)和肾上腺髓质素(ADM)是人类强有力的血管扩张剂，应用CGRP可改善心肌缺血。心脏中已发现CGRP和ADM的受体。受体活性修饰蛋白(RAMP)决定降钙素受体样受体(CRLR)的配基特异性；RAMP1和CRLR的共同表达导致CGRP受体，而RAMP2或RAMP3与CRLR的结合则产生ADM受体。由于CGRP和ADM在心力衰竭中可能起到有益的作用，我们研究了CGRP和ADM受体在慢性心力衰竭中是否上调。采用半定量逆转录聚合酶链式反应(RT-PCR)和免疫印迹分析(Western-Blot)技术，检测和定量检测了主动脉结扎后6个月心衰大鼠心房和心室组织中RAMP1和RAMP3mRNA和蛋白的表达。我们的结果首次显示，在这种心力衰竭模型中，RAMP1和RAMP3的mRNAs和蛋白质表达上调。编码CRLR、RAMP2、RDC1(犬孤儿受体)和ADM的mRNAs没有变化。本研究结果提示，在成年大鼠充血性心力衰竭后，心房和心室的CGRP受体(与CRLR相关的RAMP1增加)和ADM受体(与CRLR相关的RAMP3表达增加)表达上调。这些发现支持CGRP和ADM受体在大鼠慢性心力衰竭中的代偿作用。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators in humans and improved myocardial ischemia is observed after CGRP administration. Receptors for CGRP and ADM were already identified in heart. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart failure, we investigated whether the CGRP and ADM receptors are upregulated in chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in both atria and ventricles of failing hearts 6 months after aortic banding in rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3 mRNAs and proteins in this model of cardiac failure. No change was observed in mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present results suggested after congestive heart failure in adult rats, an up-regulation of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in atria and ventricles and of ADM receptor (by increased RAMP3 expression that is associated with CRLR) in atria. These findings support a functional role for CGRP and ADM receptors to compensate the chronic heart failure in rats. (C) 2002 Elsevier Science (USA). All rights reserved.